Dopamine agonists have been used as first or adjunctive therapy for acromegaly for many years, but relatively few studies have assessed the efficacy of a newer agonist, cabergoline (CAB) alone or in combination with somatostatin analogues (SSA). The aim of this study was to evaluate the efficacy of combined treatment with SSA plus CAB in patients with acromegaly and resistance to SSA, defined as lack of normalization of IGF-I levels after long-term (>1 year) and high dose (30 mg/month) treatment with SSA. Twelve patients (8 men and 4 women, age 3270 years) with active acromegaly after unsuccessful surgery entered the study: 10 patients had been treated with octreotide LAR and 2 with lanreotide; 7 had a pituitary macroadenoma, 2 a microadenoma and 3 an empty sella. None of the patients had hyperprolactinemia. CAB was added at the initial dose of 1 mg/week for 1 month, then increased to 3.5 mg/week. After long-term SSA treatment, no significant difference in GH (P=0.56) and IGF-I (P=0.08) levels was found, whereas tumor volume was significantly reduced (P=0.014) as compared to baseline. After 6-month treatment with SAA plus CAB, both GH (P=0.004) and IGF-I (P=0.005) levels as well as tumor volume (P=0.014) were significantly decreased compared to baseline. Moreover, GH (P=0.02) and IGF-I (P=0.002) levels, as well as tumor volume (P=0.014), measured after SAA plus CAB treatment were also significantly lower than those measured after SSA treatment alone. The addition of CAB to SSA induced a percent GH, IGF-I and tumor volume decrease of 46±41%, 24±23% and 17±37% respectively. After six months of combined treatment, six patients (50%) showed a normalization of GH and IGF-I levels. In conclusion, combined treatment with SAA plus CAB can be effective in inducing IGF-I normalization in acromegalic patients resistant to SSA and deserves an important role as alternative treatment in the therapeutic algorithm of acromegaly.